Cisplatin is indicated as first line therapy for lung cancer, head & neck cancer and for the treatment of advanced and metastatic ovarian carcinoma, bladder carcinoma and testis carcinoma.
Cisplatin is a platinum compound of which only the cis-isomer is active. It appears to produce intra-and interstrand cross links which modify DNA structure and inhibit DNA synthesis. In addition and to a lesser extent Cisplatin inhibits protein and RNA synthesis. It does not appear to be phase-specific in the cell cycle.
Metastatic ovarian cancer: As monotherapy: 100 mg/m2 per cycle, given as a single dose infused in 0.9% sodium chloride or glucose once every 4 wk. For combination therapy with cyclophosphamide: 75-100 mg/m2 on day 1 of every 4-wk cycle. Metastatic testicular tumours: 20 mg/m2 BSA daily for 5 days per cycle. Advanced bladder cancer: 50-70 mg/m2 per cycle once every 3-4 wk, depending on the extent of prior exposure to radiation and/or chemotherapy treatment. An initial dose of 50 mg/m2 every 4 wk may be used in heavily pre-treated patients. Usual dosage and schedule: 40 to 120 mg/m2 I.V. on day 1 as infusion every 3 weeks. 15 to 20 mg/m2 I.V. on days 1 to 5 as infusion every 3 to 4 weeks. The usual dose in adults and children when used as single agent therapy is 50-100 mg/m2.
Cisplatin is mostly used in combination with antineoplastic drugs having similar cytotoxic effects. In these circumstances additive toxicity is likely to occur. Other known drug interactions are reported below:
Nephrotoxic drugs: Aminoglycoside antibiotics, when given concurrently or within 1-2 weeks after Cisplatin administration, may potentiate its nephrotoxic effects. Concomitant use of other potentially nephrotoxic drugs (eg Amphotericin B) is not recommended during Cisplatin therapy.
Ototoxic drugs: Concurrent and/or sequential administration of ototoxic drugs such as aminoglycoside antibiotics or loop diuretics may increase the potential of Cisplatin to cause ototoxicity, especially in the presence of renal impairment.
Renally excreted drugs: Cisplatin may alter the renal elimination of bleomycin and methotrexate (possibly as a result of Cisplatin-induced nephrotoxicity) and enhance their toxicity.
Anticonvulsant agents: In patients receiving Cisplatin and Phenytoin, serum concentrations of the latter may be decreased, possibly as a result of decreased absorption and/or increased metabolism. In these patients, serum levels of phenytoin should be monitored and dosage adjustments made as necessary.
Antigout agents: Cisplatin may raise the concentration of blood uric acid. Thus, in patients concurrently receiving antigout agents such as Allopurinol, Colchicine, Probenecid or Sulfinpyrazone, dosage adjustment of these drugs may be necessary to control hyperuricemia and gout.
Cisplatin is contraindicated in patients with pre-existing renal impairment. Cisplatin should not be employed in myelosuppressed patients, or patients with hearing impairment. It is also contraindicated in patients with a history of allergic reactions to cisplatin or other platinum-containing compounds. Patients with renal or hepatic disorder, myelosuppression. Monitor renal, neurological and auditory function. Perform blood counts regularly. Maintain adequate hydration before and 24 hr after admin to minimise nephrotoxicity.
Severe nausea and vomiting. Serious toxic effects on the kidneys, bone marrows and ears. Hypomagnesaemia, hypocalcaemia, hyperuricaemia. Peripheral neuropathies, papilloedema, optic neuritis, seizures. Ototoxicity (children) manifested as tinnitus, loss of hearing, deafness or vestibular toxicity.
Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Acute overdosage with this drug may result in kidney failure, liver failure, deafness, ocular toxicity (including detachment of the retina), significant myelosuppression, intractable nausea and vomiting and/or neuritis. In addition, death can occur following overdosage. No proven antidotes have been established for Cisplatin overdosage. Hemodialysis, even when initiated four hours after the overdosage, appears to have little effect on removing platinum from the body because of Platinol's rapid and high degree of protein binding. Management of overdosage should include general supportive measures to sustain the patient through any period of toxicity that may occur.
Store the vial in original carton at 25°C. Do not refrigerate. Protect from light and keep out of the reach of children.
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